CVM-1118 in Combination With Nivolumab for Unresectable Advanced Hepatocellular Carcinoma

NCT ID: NCT05257590

Last Updated: 2025-12-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

95 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-05-23

Study Completion Date

2026-03-31

Brief Summary

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CVM-1118 is a new small molecule chemical entity being developed as a potential anti-cancer therapeutic by TaiRx, Inc. CVM-1118 is a potent anti-cancer agent in numerous human cancer cell lines. The safety of administrating CVM-1118 on human has been evaluated from the phase 1 study. The objective of the phase 2 study is to further investigate the efficacy of CVM-1118 with nivolumab for subjects with unresectable advanced hepatoma.

Detailed Description

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Nivolumab, a human IgG4 kappa monoclonal antibody acts as a checkpoint inhibitor, blocking the interaction between PD-1 and its ligands (PD-L1 and PD-L2 ) and therefore preventing the activation of T cells from attacking the cancer. Nivolumab is currently approved for several cancer types.

To meet the medical need, TaiRx, Inc. develops a new small molecule drug, CVM-1118 can promote apoptosis and delay proliferation. Moreover, CVM-1118 targets the formation of vasculogenic mimicry (VM). VM has been associated with tumor metastasis and poor clinical outcomes. VM is reported to be particularly active in tumor under hypoxia state when patients are treated with the potent vascular endothelial growth factor (VEGF) inhibitor like sorafenib or bevacizumab. Hence, the ability of inhibiting the VM network makes CVM-1118 a potential good combination drug with Nivolumab in advanced diseases such as hepatoma where Nivolumab alone has shown activity.

The safety profile of CVM-1118 dosing has been established in the phase 1 study. The analysis of metabolism pathways further showed that the potential drug-drug interactions of CVM-1118 and Nivolumab are very low.

Based on the mechanism of actions and the safety analysis of nivolumab and CVM-1118, the design of phase 2 trial with the combination therapy might have great potential for the patients with unresectable advanced HCC.

Conditions

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Hepatocellular Carcinoma Advanced Cancer

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Nivolumab + CVM-1118

1 Cycle = 28 days

Nivolumab, 240 mg, IV, Q2 weeks with an option for 480 mg, IV, Q4 weeks starting from Cycle 3 if judged to be reasonable by the investigator based on the safety and tolerability.

CVM-1118, 200 mg, PO, BID with an option to increase the starting dose to 300 mg, PO, BID for the subsequent subjects following assessment of safety data from the initial 10 subjects. Escalation of the starting dose will be dependent on the absence of Dose Limiting Toxicity in at least 7 of the initial 10 subjects treated at 200 mg, PO, BID.

Individual subjects receiving a starting dose of 200 mg, PO, BID and who tolerate the initial 2 cycles with no more than Grade 2 related toxicity, will have the option of increasing their dose of CVM-1118 to 300 mg, PO, BID (600 mg total daily dose) starting with cycle 3

Tolerable dose of Nivolumab and CVM-1118 will be administered continuously for a 28-day cycle until progressive disease, unacceptable toxicity, or consent withdrawal.

Group Type EXPERIMENTAL

Nivolumab Injection [Opdivo]

Intervention Type DRUG

Nivolumab will be administered at 240 mg, IV, Q2 weeks with an option for 480 mg, IV, Q4 weeks starting with Cycle 3 if judged to be reasonable by the investigator based on the safety and tolerability.

CVM-1118

Intervention Type DRUG

CVM-1118 will be administered 200 mg, PO, BID with an option to increase the starting dose to 300 mg, PO, BID for the subsequent subjects following assessment of safety data from the initial 10 subjects.

Interventions

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Nivolumab Injection [Opdivo]

Nivolumab will be administered at 240 mg, IV, Q2 weeks with an option for 480 mg, IV, Q4 weeks starting with Cycle 3 if judged to be reasonable by the investigator based on the safety and tolerability.

Intervention Type DRUG

CVM-1118

CVM-1118 will be administered 200 mg, PO, BID with an option to increase the starting dose to 300 mg, PO, BID for the subsequent subjects following assessment of safety data from the initial 10 subjects.

Intervention Type DRUG

Other Intervention Names

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Nivolumab TRX-818

Eligibility Criteria

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Inclusion Criteria

* Age 18+ (20+ for subjects in Taiwan)
* Diagnosis of hepatocellular carcinoma

* Pathologically or cytologically-confirmed or clinically diagnosed in accordance with American Association for the Study of Liver Diseases (AASLD) criteria (i.e., radiologic imaging with cross-sectional multiphasic contrast CT or MRI showing a ≥ 1 cm liver lesion)
* Subjects with advanced-stage, unresectable hepatocellular carcinoma that is not appropriate for potentially curable therapy who have progressed from, been intolerant of prior systemic anti-cancer therapies (e.g., sorafenib, lenvatinib, atezolizumab in combination with bevacizumab).
* Barcelona Clinic Liver Cancer (BCLC) stage B not appropriate for or with disease progression after local regional therapy, or BCLC stage C
* Child-Pugh liver function class A
* Measurable disease (per mRECIST)
* ECOG performance status of 0 to 1
* Adequate laboratory parameters including:

* AST and ALT ≤ 3.0 x ULN (≤ 5.0 x ULN if due to liver involvement)
* Total serum bilirubin ≤ 2.0 x ULN (≤ 3.0 x ULN for subjects with documented Gilbert's syndrome)
* ANC ≥1500/µL
* Platelets ≥ 90,000/µL
* HGB ≥ 9.0 g/dL
* Serum creatinine clearance of ≥ 50 mL/min based on Cockcroft-Gault formula
* Serum albumin ≥ 2.8 gm/dL
* INR ≤ 2.3
* PT/aPTT ≤ 1.2 x ULN
* QTcF ≤ 480 msec
* Subjects are eligible to enroll if they have HBV-, or HCV-HCC, defined as follows:

* Chronic HBV infection as evidenced by detectable HBV DNA or HBsAg. Subjects with chronic HBV infection must be on antiviral therapy and have HBV DNA \<500 IU/mL. If not on an antiviral therapy at screening, then subjects must be willing to start the antiviral therapy at the time of consent.
* Active or resolved HCV infection as evidenced by detectable HCV RNA or antibody.

Exclusion Criteria

* HCC with portal vein invasion at the main portal branch (Vp4)
* Known history of esophageal varices or gastrointestinal bleeding within the past 3 months
* Prior immunotherapy for hepatoma
* ≤ 7 days from prior limited field palliative irradiation therapy and C1D1
* ≤ 28 days from prior irradiation therapy and C1D1
* ≤ 14 days (or 5 half-lives) from prior systemic anticancer therapy and C1D1
* ≤ 28 days from local regional therapy (e.g., trans-arterial embolization, radiofrequency ablation) and C1D1
* Presence of other active cancer(s) likely to require treatment in the next two (2) years or likely to impact the assessment of any study endpoints
* Active bacterial or fungal infection(s) requiring systemic therapy within 7 days prior to C1D1
* Known CNS metastases
* Known history of HIV infection
* Females who are currently pregnant or breast-feeding
* Known gastrointestinal disease that may significantly alter the absorption of oral medications
* Psychiatric illness or social situation that would interfere with compliance with study requirements
* History of clinically significant cardiovascular abnormalities
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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TaiRx, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Pei-Jer Chen, MD/PhD

Role: PRINCIPAL_INVESTIGATOR

National Taiwan University Hospital

Locations

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Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, , Taiwan

Site Status RECRUITING

Keelung Chang Gung Memorial Hospital

Keelung, , Taiwan

Site Status RECRUITING

National Cheng Kung University Hospital

Tainan, , Taiwan

Site Status RECRUITING

National Taiwan University Hospital

Taipei, , Taiwan

Site Status RECRUITING

Taipei Veterans General Hospital

Taipei, , Taiwan

Site Status RECRUITING

Countries

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Taiwan

Central Contacts

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Yen-Ling Chen, PhD

Role: CONTACT

886-2-2653-5007 ext. 113

Facility Contacts

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Sheng-Nan Lu, MD/Ph.D

Role: primary

Kun-Yun Yeh, MD/Ph.D

Role: primary

Yan-Shen Shan, MD/PhD

Role: primary

Pei-Jer Chen, MD/PhD

Role: primary

Yi-Hsiang Huang, MD/PhD

Role: primary

Other Identifiers

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CVM-008

Identifier Type: -

Identifier Source: org_study_id